Identification of SopE2 from <i>Salmonella typhimurium</i>, a conserved guanine nucleotide exchange factor for Cdc42 of the host cell

Stender, Silke; Friebel, Andrea; Linder, Stefan; Rohde, Manfred; Mirold, Susanne; Hardt, Wolf‐Dietrich

doi:10.1046/j.1365-2958.2000.01933.x

Cited by 270 publications

(318 citation statements)

References 49 publications

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“…It is common that a bacterial pathogen codes for numerous effectors but the presence of multiple paralogs of a specific translocated effector in the same organism is only occasionally found (28)(29)(30). The close similarity among proteins in a family points to functional redundancy, which may provide an explanation for the failure to identify these proteins in previous genetic screens for bacterial mutants defective in intracellular growth.…”

Section: Discussionmentioning

confidence: 99%

Multiple substrates of the Legionella pneumophila Dot/Icm system identified by interbacterial protein transfer

Luo

Isberg

2004

Proc. Natl. Acad. Sci. U.S.A.

460

549

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Legionella pneumophila is an intracellular pathogen that multiplies in a specialized vacuole within host cells. Biogenesis of this vacuole requires the Dot͞Icm type IV protein translocation system. By using a Cre͞loxP-based protein translocation assay, we found that proteins translocated by the Dot͞Icm complex across the host phagosomal membrane can also be transferred from one bacterial cell to another. The flexibility of this system allowed the identification of several families of proteins translocated by the Dot͞Icm complex. When analyzed by immunofluorescence microscopy, a protein identified by this procedure, SidC, was shown to translocate across the phagosomal membranes to the cytoplasmic face of the L. pneumophila phagosome. The identification of large numbers of these substrates, and the fact that the absence of any one substrate rarely results in strong defects in intracellular growth, indicate that there is significant functional redundancy among the Dot͞Icm translocation targets.bacterial pathogenesis ͉ protein translocation ͉ plasmid conjugation A ctive modification of host cellular functions is essential for a bacterial pathogen to establish a successful infection. Such modification often is mediated by injecting effectors into the host cytoplasm through specialized protein secretion systems (1). Among these systems, conjugation-adaptive transporters, also called type IV secretion systems (TFSS), have been identified in a number of bacterial pathogens (2). Many of these TFSS are dedicated DNA transfer apparatuses, whereas others allow Gram-negative bacterial pathogens to translocate protein substrates directly into the cytosol of eukaryotic cells. Only a few protein substrates of TFSS that are translocated into host cells have been identified (2).Legionella pneumophila is an intracellular pathogen that causes Legionnaire's disease. After being phagocytosed by macrophages, the bacteria multiply within a specialized vacuole that is initially isolated from the endocytic pathway (3, 4), possibly by intercepting early secretory vesicles (5). Biogenesis of this replicative phagosome requires the TFSS transporter called Dot͞ Icm (6, 7). Substrates transported by this apparatus are believed to directly promote the targeting pathway of the bacterial vacuole (8). Two of these substrates, RalF and LidA, have been identified (9, 10). RalF is a guanine nucleotide exchange factor for multiple Arf proteins (9), whereas the biochemical activity of LidA is unknown (10). There are clearly other unidentified substrates of Dot͞Icm, as mutations that specifically eliminate LidA cause negligible defects in intracellular growth and mutations in ralF are proficient for intracellular replication (9, 10). A comprehensive analysis of the identity and function of effectors translocated by the Dot͞Icm apparatus is crucial in determining how this bacterium establishes a replication vacuole. We report here that proteins translocated from bacteria to host cells can also be transferred between bacterial cells, allowing identificat...

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Section: Discussionmentioning

confidence: 99%

Multiple substrates of the Legionella pneumophila Dot/Icm system identified by interbacterial protein transfer

Luo

Isberg

2004

Proc. Natl. Acad. Sci. U.S.A.

460

549

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“…SopE, SopE2, and SopB do not directly interact with actin but mediate the activation of small GTPases of the Rho family that are required for the formation of highly branched actin networks. As explained in the last section of this paper, SopE and SopE2 mimic mammalian guanine nucleotide exchange factors (GEFs) to activate the GTPases Rac1 and Cdc42 by catalyzing exchange of GDP for GTP [25,26], whereas SopB indirectly activates RhoG targeting its GEF, SGEF [27]. After bacteria entry, membrane ruffling is terminated by the GTPase-activating protein (GAP) activity of SptP that inactivates Rac1 and Cdc42, reverting the actin cytoskeleton to its basal state after bacteria entry [28].…”

Section: Actin Cytoskeleton and Invasionmentioning

confidence: 99%

Impact ofSalmonella entericaType III Secretion System Effectors on the Eukaryotic Host Cell

Ramos‐Morales

2012

ISRN Cell Biology

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Type III secretion systems are molecular machines used by many Gram-negative bacterial pathogens to inject proteins, known as effectors, directly into eukaryotic host cells. These proteins manipulate host signal transduction pathways and cellular processes to the pathogen's advantage. Salmonella enterica possesses two virulence-related type III secretion systems that deliver more than forty effectors. This paper reviews our current knowledge about the functions, biochemical activities, host targets, and impact on host cells of these effectors. First, the concerted action of effectors at the cellular level in relevant aspects of the interaction between Salmonella and its hosts is analyzed. Then, particular issues that will drive research in the field in the near future are discussed. Finally, detailed information about each individual effector is provided.

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“…Salmonella delivers three distinct effector proteins that functionally converge at the level of Rho family GTPases to elicit host cell entry. SopE and its homolog SopE2 act as bona fide GEFs for the Rho family members Cdc42, Rac and RhoG (Bakshi et al, 2000;Hardt et al, 1998;Stender et al, 2000). A second effector protein, SopB, encodes a phosphoinositide phosphatase that feeds into the GTPase cycle by indirectly activating a host-encoded exchange factor, SGEF, specific for RhoG (Patel and Galan, 2006).…”

Section: Introductionmentioning

confidence: 99%

Investigating the Function of Rho Family GTPases during Salmonella/Host Cell Interactions

Patel¹,

Galán²

2008

Methods in Enzymology

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Salmonella enterica comprise a family of pathogenic gram-negative bacteria that have evolved sophisticated virulence mechanisms to enter non-phagocytic cells. The entry event is the result of a carefully orchestrated modulation of Rho family GTPase activity within the host cell, which in turn triggers localized remodeling of the actin cytoskeleton. These cytoskeletal rearrangements drive profuse membrane ruffling and lamellipodial extensions that envelop bacteria and trigger their internalization. This chapter describes a number of methods used to investigate the role of Rho family GTPases during Salmonella/host cell interactions. In particular, we detail a variety of complementary techniques, including affinity pull-down assays and bacterial-induced membrane ruffling and internalization assays to show that Salmonella-induced actin remodeling and entry require the Rho family members Rac and RhoG.

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Identification of SopE2 from Salmonella typhimurium, a conserved guanine nucleotide exchange factor for Cdc42 of the host cell

Cited by 270 publications

References 49 publications

Multiple substrates of the Legionella pneumophila Dot/Icm system identified by interbacterial protein transfer

Multiple substrates of the Legionella pneumophila Dot/Icm system identified by interbacterial protein transfer

Impact ofSalmonella entericaType III Secretion System Effectors on the Eukaryotic Host Cell

Investigating the Function of Rho Family GTPases during Salmonella/Host Cell Interactions

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